The present invention relates to a sulfate of 5,6,7,8-tetrahydro-L-erythro-biopterin (hereinafter referred to as "tetrahydrobiopterin") and a process for preparing the same.
In a living body, it has been well known that (6R)-tetrahydrobiopterin has a very important role as a coenzyme in a catecholamine-serotonin synthesis. Recently, the importance of (6R)-tetrahydrobiopterin has been recognized in the course of the fundamental study thereon. It has been expected that (6R)-tetrahydrobiopterin can be widely used for a treatment of patients with Parkinson's disease or depression as well as phenylketonuria which has been conventionally treated with (6R)-tetrahydrobiopterin.
In general, (6R)-tetrahydrobiopterin is synthesized by catalytically hydrogenating L-erythrobiopterin. In accordance with a conventional reaction condition, however, the (6S)-form being not present in nature is produced as a by-product at about 50% of the (6R)-form. Although a mixture of the (6R)-form and the (6S)-form hitherto has been obtained as a hydrochloride, it is difficult to separate the hydrochloride into each of its isomers by means of fractional crystallization. This is due to the poor crystallinity of tetrahydrobiopterin hydrochloride.
Then, there are proposed various methods, for instance, a method for separating the (6R)-form from the (6S)-form by employing high performance liquid chromatography (hereinafter referred to as "HPLC" (S. W. Baily et. al., "J. Biological Chem., 253, 1598 (1978); or Matsuura et. al., "J. Biochem." 87, 951 (1980)); a method in which the (6R)-form is obtained by means of fractional crystallization of polyacylated tetrahydrobiopterin such as 2-N-acetyl 5,8-di-N-acetyl-1',2'-di-O-acetyl-5,6,7,8-tetrahydrobiopterin (M. Viscontini et. al., "Helv. Chim. Acta., 65, 1090 (1982)); and the like. However, a separating method by HPLC cannot be employed on an industrial scale, and in the fractional crystallization of polyacylated tetrahydrobiopterin, there are problems in that many reaction steps are required and the yield of the (6R)-form is low. Therefore, these methods are not utilizable.
An object of the present invention is to provide an easy process for preparing (6R)-tetrahydrobiopterin.
A further object of the present invention is to obtain the (6R)-form in a high yield.